Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages

Antonio Iavarone, Emerson R. King, Xu Ming Dai, Gustavo Leone, E. Richard Stanley, Anna Lasorella

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

In mammals, the fetal liver is the first site of definitive erythropoiesis-the generation of mature, enucleated red cells. The functional unit for definitive erythropoiesis is the erythroblastic island, a multicellular structure composed of a central macrophage surrounded by erythroblasts at various stages of differentiation. Targeted disruption of the retinoblastoma (Rb) tumour suppressor gene in the mouse leads to embryonic death caused by failure of erythroblasts to enucleate. The erythroid defect has been attributed to loss of Rb in cells that support erythropoiesis, but the identity of these cells is unknown. Here we show that Rb-deficient embryos carry profound abnormalities of fetal liver macrophages that prevent physical interactions with erythroblasts. In contrast, wild-type macrophages bind Rb-deficient erythroblasts and lead them to terminal differentiation and enucleation. Loss of Id2, a helix-loop-helix protein that mediates the lethality of Rb-deficient embryos, rescues the defects of Rb-deficient fetal liver macrophages. Rb promotes differentiation of macrophages by opposing the inhibitory functions of Id2 on the transcription factor PU.1, a master regulator of macrophage differentiation. Thus, Rb has a cell autonomous function in fetal liver macrophages, and restrains Id2 in these cells in order to implement definitive erythropoiesis.

Original languageEnglish (US)
Pages (from-to)1040-1045
Number of pages6
JournalNature
Volume432
Issue number7020
DOIs
StatePublished - Dec 23 2004

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages'. Together they form a unique fingerprint.

  • Cite this

    Iavarone, A., King, E. R., Dai, X. M., Leone, G., Stanley, E. R., & Lasorella, A. (2004). Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages. Nature, 432(7020), 1040-1045. https://doi.org/10.1038/nature03068